UNDERSTANDING HOW THE BRAIN receives information from the environment and processes it to make decisions is a major challenge in neuroscience. The prize winners have addressed this question in different organisms, from worms to primates. They have used a wide range of approaches and have invented new technologies.

Cornelia Bargmann has pioneered the study of how genetic programs control the operation of neural circuits. By exploiting the simplicity of the C. elegans nervous system, Bargmann has identified fundamental principles of neural circuit logic. The functional circuits involve fast synaptic transmission and volume transmission via amines and peptides as well as gap junctions – much like our nervous system – but are more amenable to genetic analysis. She provided the first evidence, in any animal, for the detailed neuronal pathway between a specific sensory receptor protein and behaviour.

Winfried Denk has devised two experimental innovations of broad impact to studies of how individual neurons respond to synaptic inputs. He developed multi-photon microscopy, which revolutionized high resolution imaging in the living brain. Using this technique, he discovered that direction selectivity is computed locally in individual dendritic branches of starburst amacrine cells in the retina. His invention of serial block-face scanning electron microscopy then revealed the wiring asymmetry between these inter-neurons and the retinal ganglion cells that convey motion information to the brain.

Ann Graybiel has unravelled the modular architecture of the striatum, and discovered striatal plasticity underlying habit learning. Her detailed analysis of how multiple cortico-striatal loops change when animals learn new skills reveals the way neuronal circuits organize familiar motor patterns into action sequences. The cortico-striatal associative loops are also important for working memory and cognitive control, and likely contribute to the mechanism of disorders such as schizophrenia, Parkinson’s disease and addiction.